Gastrointestinal clear cell sarcoma (GICCS)/malignant gastrointestinal neuroectodermal tumor (GNET) is an extremely rare form of cancer with aggressive clinical behavior. It has distinct pathological, immunohistochemical, ultrastructural, and molecular features. Herein, we present the case of a 20-year-old woman with no notable medical history who presented to the outpatient department with complaints of abdominal pain and vomiting. Symptoms had been evolving for 3 months. The physical examination revealed slight abdominal tenderness and melena. Biological investigations revealed iron-deficiency anemia. The upper and lower endoscopies showed no abnormalities. Magnetic resonance enterography revealed small bowel wall thickening of 15 mm × 2 mm. Exploratory laparotomy revealed an ileal mass with mesenteric lymphadenopathy. A wide resection of the mass was then performed. The final pathological report confirmed the diagnosis of small bowel GICCS/GNET. After 11 months of follow-up, the patient presented with mesenteric lymph node metastases.

Malignant gastrointestinal neuroectodermal tumors (GNETs) are rare aggressive malignant neoplasms that exclusively occur within the wall of the gastrointestinal tract. The GNET was first described as an \'osteoclast-rich tumor of the gastrointestinal tract with features resembling clear cell sarcoma (CCS) of soft parts\' in 2003. Although the GNET shares certain histological features with CCS, it is characterized by a lack of melanocytic differentiation and the presence of non-tumoral osteoclast-like giant cells (OLGCs). The present study reports a case of a GNET of the ileum with intra-abdominal granulomatous nodules, an uncommon accompanying finding, and summarizes the current literature. A 30-year-old woman presented with the symptoms of intestinal obstruction, and a mass was found within the ileum wall. Multiple grey-white nodules were found adhering to the omentum and serosa of the ileum. Histologically, the tumor was located in the muscularis propria and infiltrated the mucosa and the serosa. Tumor cells presented with oval or polygonal nuclei and prominent nucleoli, and were predominantly arranged in nested and pseudopapillary patterns, with the presence of cluster of differentiation (CD)68-positive, scattered OLGC. Immunohistochemically, it was determined that the tumor cells expressed Vimentin, CD56, S-100 and transcription factor SOX-10, while being negative for pan-cytokeratin, cytokeratin (CK)7, CK20, synaptophysin, chromogranin-A, CD117, anoctamin-1, CD34, human melanoma black-45, Melan-A, smooth muscle actin, CD3 and CD20 expression. Ewing sarcoma breakpoint region 1 gene rearrangement was identified by fluorescence in situ hybridization analysis. Ultrastructurally, no typical melanosomes were identified. In addition, the intra-abdominal grey-white nodules were microscopically identified as chronic granulomatous inflammation. The patient received four cycles of adjuvant chemotherapy following routine tumor resection. Due to its rarity and histological similarity with other neoplasms, unfamiliarity with the features of GNETs by surgical pathologists can easily lead to a misdiagnosis. Therefore, comprehensive assessments, including morphology and ancillary studies, are required for an accurate diagnosis of GNET.

BACKGROUND: Malignant gastrointestinal neuroectodermal tumor (GNET) is an extremely rare entity that was first described by Zambrano et al. in 2003 as \"Clear cell sarcoma-like tumor of the gastrointestinal tract\". It shares some of the histological features of clear cell sarcoma (CCS) but lacks the immunohistochemical reactivity for melanocytic markers. We report a case of GNET that was initially misdiagnosed as gastrointestinal stromal tumor (GIST). Recognizing this entity is important to avoid misdiagnosis.
METHODS: A case of an 18-year-old male presented with a small intestinal tumor. Histologically it was characterized by polygonal cells arranged in pseudoalveolar pattern and situated in the muscularis propria. Scattered osteoclast-like multinucleated giant cells were also noted. The neoplastic cells were positive for S-100 protein and negative for HMB-45, Melan A, smooth muscle actin, desmin and CD117. EWSR1 gene rearrangement was detected by fluorescence in situ hybridization (FISH) analysis. The patient returned with recurrence after 36 months\' management by surgical resection and died one year later.
CONCLUSIONS: GNET can be mistaken histologically for other non-epithelial gastrointestinal tumors. Awareness of its existence and diagnostic criteria by the pathologist is necessary to avoid misdiagnosis, particularly as GIST, CCS or malignant peripheral nerve sheath tumor (MPNST).

Malignant gastrointestinal neuroectodermal tumor (GNET) is a rare soft tissue sarcoma, previously referred to as clear cell sarcoma-like gastrointestinal tumor (CCSLGT) and also commonly reported in the literature as clear cell sarcoma of the gastrointestinal tract (CCS-GI). The current study reports a case of GNET arising in the stomach of a 17-year-old male, who presented with symptoms of fatigue, anemia and low temperature. Examination with positron emission tomography-computed tomography revealed a soft tissue mass in the gastric antrum. Subsequently, radical distal gastric resection was performed, and the mass measured 6.0×4.0×3.5 cm3. Histopathological analysis revealed that the tumor cells were arranged in nests and focally formed fascicular, pseudopapillary, pseudoalveolar and rosette-like growth patterns. Osteoclast-like giant cells were also observed. Immunohistochemically, the tumor cells were positive for S-100 protein, vimentin and BCL-2, and negative for HMB45, Melan-A, CD117, CD34 and CD99. Additionally, the osteoclast-like giant cells were positive for CD68. Fluorescence in situ hybridization demonstrated EWSR1 gene rearrangement. After 10 months of follow-up, no evidence of recurrence or metastasis was observed. As GNET is currently classified differently and under various names in the literature, the information provided by this case study and review is predicted to be useful towards the accurate diagnosis, treatment and prognosis of this rare tumor type.